A Pilot Study of CD19-Specific Car T Cells as Consolidation for Older Adults With Acute Lymphoblastic Leukemia in First Remission
概览
- 阶段
- 1 期
- 干预措施
- Biospecimen Collection
- 疾病 / 适应症
- B Acute Lymphoblastic Leukemia
- 发起方
- City of Hope Medical Center
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence of dose-limiting toxicity (DLT)
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
This phase I trial tests the safety, side effects, and best dose of autologous anti-CD19 CAR-expressing T lymphocytes (CD19-CAR T cells) in older adults with B-cell acute lymphoblastic leukemia. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of B-cell acute lymphoblastic leukemia.
详细描述
PRIMARY OBJECTIVE: I. Assess the safety and tolerability of autologous CD19-CAR T cell therapy by evaluation of toxicities including type, frequency, severity, attribution, time course and duration in older patients with B-cell acute lymphoblastic leukemia (ALL) in first morphological complete remission (CR1). SECONDARY OBJECTIVES: I. Assess the feasibility of manufacturing and infusing CD19-CAR T cells in older adults with B-cell ALL in CR1. II. Evaluate the rate of MRD- remission in patients who had MRD+ disease at the time of infusion. III. Evaluate the overall risk of relapse. IV. Evaluate the risk of central nervous system (CNS) relapse (isolated and combined with bone marrow relapse). V. Estimate the 1-year event-free survival (EFS) rate post CD19-CAR T cell therapy. VI. Estimate 1-year overall survival (OS) post CD19-CAR T cell therapy. VII. Describe development of frailty after CD19-CAR T cell therapy. EXPLORATORY OBJECTIVES: I. Measure expansion and persistence of CD19-CAR T cells in peripheral blood (PB), bone marrow (BM) and cerebrospinal fluid (CSF). II. Assess the duration of B-cell aplasia. III. Describe cytokine levels in PB over the study period. OUTLINE: This is a dose-escalation study of CD19-CAR T cell therapy followed by a dose-expansion study. Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide intravenously (IV), and then receive CD19-CAR T cell infusion IV on study.
研究者
入排标准
入选标准
- •Documented informed consent of the participant
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- •If unavailable, exceptions may be granted with Study Principal Investigator (PI) approval
- •Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
- •Age: \>= 55 years
- •Eastern Cooperative Oncology Group (ECOG) \< 2 / Karnofsky Performance Status (KPS) \>= 70
- •Ability to read and understand English for Questionnaires
- •Histologically confirmed CD19+ ALL at the time of diagnosis
- •In morphological first complete remission regardless of minimal residual disease (MRD) status
- •No immediate plan for transplant
排除标准
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent(s)
- •Research participant with known CNS-2 or CNS-3 involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation. Research participants with a history of central nervous system (CNS) disease that has been effectively treated to complete remission (\<5 WBC/mm3 and no blasts in cerebrospinal fluid \[CSF\]) will be eligible
- •Autoimmune disease or active graft versus host disease (GVHD) requiring systemic immunosuppressant therapy
- •Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
- •History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for \>= 2 years
- •Clinically significant uncontrolled illness
- •Active systemic uncontrolled infection requiring antibiotics
- •Known history of HIV or hepatitis B or hepatitis C infection
- •Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
- •Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core Ab positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment
研究组 & 干预措施
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Biospecimen Collection
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Bone Marrow Aspiration and Biopsy
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Leukapheresis
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Autologous Anti-CD19 CAR-expressing T Lymphocytes
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Questionnaire Administration
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Cyclophosphamide
Treatment (CD19-CAR T cells)
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.
干预措施: Fludarabine
结局指标
主要结局
Incidence of dose-limiting toxicity (DLT)
时间窗: Up to 28 days after CD19-chimeric antigen receptor (CAR) T cell infusion
Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, and reversibility or outcome.
Incidence of adverse events
时间窗: Up to 15 years
Assessed using CTCAE version 5.0. Cytokine release syndrome adverse events will be characterized using the descriptions and grading scales found in the Lee, et. al. publication: 'ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, and reversibility or outcome.
次要结局
- Minimal residual disease (MRD) response rate(Up to 12 months post T cell infusion)
- Event-free survival(From the start of CD19-CAR T cell infusion to the date of death or disease progression/relapse, whichever occurring first, assessed up to 15 years)
- Percentage of consented older B-acute lymphoblastic leukemia (ALL) patients undergoing leukapheresis who get sufficient CD19-CAR T cells manufactured and infused at their assigned dose level(At T cell infusion (Day 0))
- Overall survival rate(From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years)
- Rate of relapse, including MRD and extramedullary relapse(Up to 2 years post treatment)
- Frailty phenotype score(Pre-CAR T and at day 100)